Hello everyone. Thank you for joining me. I'm here today to highlight two important FDA updates that have significant implications for how we practice as oncology APPs caring for our patients with colorectal cancer.

The first is an exciting advancement in the world of precision oncology. In February of 2026, the FDA granted approval to encorafenib in combination with cetuximab and 5-FU-based chemotherapy in the first line setting for patients with metastatic colorectal cancer harboring BRAF V600E mutations. This builds upon the previously accelerated approval granted in December of 2024 and represents an important advancement for a patient population that we know historically has been associated with aggressive disease and poor outcomes. The approval was supported by the Phase 3 BREAKWATER data, patients receiving encorafenib, cetuximab, and FOLFOX versus standard chemo plus or minus bevacizumab had a median progression-free survival of 12.8 months compared to 7.1 months, and an improvement in median overall survival from 15.1 to 30.3 months. That's a near doubling of overall survival. We also saw improved response rate, longer duration of response, and a near 50% reduction in death events. It's also important to note while this initial approval used a FOLFOX chemotherapy backbone, additional expanded approval included FOLFIRI as the chemotherapy backbone, giving us even greater flexibility when treating this patient population. As oncology APPs, I think this further reinforces the importance of obtaining comprehensive molecular profiling early in metastatic colorectal cancer. Identifying patients with BRAF E600E mutations is no longer just prognostic, but now directly informs first line treatment options.

Secondly, also in February of 2026, the FDA strengthened the product labeling for capecitabine and fluorouracil regarding the potentially life-threatening consequences of DPD deficiency. DPD is the enzyme responsible for metabolizing more than 80% of fluorouracil. Patients with certain DPD genetic variants have reduced or absent enzyme activity, placing them at substantially increased risk for severe and even fatal toxicities. These toxicities are usually early in onset and severe, including mucositis, profound diarrhea and dehydration, severe neutropenia and myelosuppression, and neurotoxicities including encephalopathy. These toxicities may even result after the first cycle of treatment. The updated labeling now includes a boxed warning and advises DPYD testing prior to initiating capecitabine or infusional 5-FU unless immediate treatment is necessary. Patients with complete DPD deficiency should generally avoid these medications as no safe dosing adjustment has been established. For patients with partial deficiencies, dosing should be individualized. Pharmacogenomic guidelines, including CPIC recommendations, can provide additional guidance for specific genotype directed dose modifications. As APPs were commonly the providers seeing these patients prior to starting chemotherapy, and with this new guideline, we need to make sure that we're incorporating DPYD testing into our pretreatment workflow. In my practice, this would include assuring single DPD testing has been completed, but also noting that DPD testing is already included on some liquid molecular profiling panels, often with a quick turnaround, further enhancing the need to make sure it's being done.

Educating patients to be on the lookout for early severe side effects and frequent check-ins or monitoring with early intervention can be crucial to ensure patients are able to safely continue on 5-FU-based therapies. And if patients do suffer suspected or confirmed severe 5-FU toxicity or overdose, urgent evaluation of the patient is necessary for treatment with the approved antidote, uridine triacetate. These two FDA updates represent complimentary advances in colorectal cancer care, one allowing us to select more effective treatment based on tumor biology, and the other allows us to better protect patients based on their individual ability to metabolize the treatment. Precision oncology now is not just about choosing the right treatment for the right tumor, but also choosing the safest treatment based on the individual patient.

Precision oncology is now not just about choosing the right treatment for the right tumor, but also choosing the safest treatment based on the individual patient.